1. Field of the Invention
The present invention is broadly concerned with improved vaccination methods for immunization against proliferative enteritis, known as ileitis, preferably porcine proliferative ileitis, which is caused by an obligate intracellular bacterium Lawsonia Intracellularis. Specifically, the invention provides for a method of providing increased protection against L. intracellularis by vaccinating young animals starting from day one (1) of age against L. intracellularis infections. Preferably the young animals are vaccinated at day 1 to day 21 of age, more preferably at day 1 to day 10 of age, even more preferably at day 1 and to day 9 of age, even more preferably at day 1 to day 6 of age, even more preferably at day 1 or 2 of age, and most preferably at day 1 of age. Specifically, said young animal is a young piglet, preferably a pre-weaned piglet.
2. Description of the Prior Art
Porcine proliferative enteritis, is a naturally occurring disease that can affect pigs from weaning to young adult stage. It has been established that the causative agent is Lawsonia Intracellularis. L. intracellularis is an obligate, intracellular bacterium which cannot be cultured by normal bacteriological methods on conventional cell-free media and has been thought to require cells for growth. S. McOrist et al., Infection and Immunity, Vol. 61, No. 19, 4286-4292 (1993) and G. Lawson et al., J. of Clinical Microbiology, Vol. 31, No. 5, 1136-1142 (1993) discuss cultivation of L. intracellularis using IEC-18 rat intestinal epithelial cell monolayers in conventional tissue culture flasks. In U.S. Pat. Nos. 5,714,375 and 5,885,823, both of which patents are hereby incorporated by reference in their entireties, cultivation of L. intracellularis in suspended host cells was described.
Pathogenic and non-pathogenic attenuated bacteria strains of L. intracellularis are well known in the art. For example, WO 96/39629 and WO 05/011731 describe non-pathogenic attenuated strains of L. intracellularis. Attenuated bacteria strains of L. intracellularis are further described in and known from WO 02/26250 and WO 03/00665.
The disease is first characterized by its gross and microscopic pathology, and later by the demonstration of the intracellular bacteria within affected cells. The characterizing pathological feature of the disease is the proliferation of immature epithelial cells in the crypts of the ileum (terminal part of the small intestine), the large intestine or both. Sections of infected tissue are characterized by a reddened thickening mucosa resembling a “garden hose,” and enteric lesions. The gut thickening ultimately prevents normal gut function, absorption capabilities, and nutrient transfer. Clinical effects of the disease are chronic weight loss, unthriftiness, diarrhea, and death. The disease is of economic importance owing to death loss, increased medication costs, poor weight gain and decreased food conversion in affected animals. Clinical cases of ileitis are observed most notably in pigs 6-20 weeks of age. However, the presence of L. intracellularis has been confirmed (PCR) in recently weaned pigs (3-4 weeks of age), suggesting L. intracellularis exposure occurs in the nursery and perhaps, originates from Lawsonia-positive dams (Mauch and Bilkei (2004) Vet Rec 155: 532; Marsteller et al. (2003). Swine Health Prod 11:127-130; Stege et al. (2004). Vet Micro 104: 197-206). These observations underline the importance for incorporating prevention strategies, such as vaccination earlier in the production system.
Current vaccination strategies for immunization against ileitis involve oral administration of the vaccine to Lawsonia-naïve pigs exclusively from three weeks of age and older, because piglets below this age group could have maternal antibodies positive for L. intracellularis due to previous sow exposure or vaccination. Prior to the method of the present invention it was believed that the presence of maternal antibodies or other lactogenic factors could potentially interfere with the efficacy of vaccinations in such piglets, because the maternal antibodies have the ability to neutralize the vaccine before the piglet's immune system can recognize it and begin secreting its own antibodies. Therefore, vaccination of young piglets has been avoided in the face of maternal immunity.